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Association of adipogenic genes with SC-35 domains during porcine adipogenesis

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Abstract

Spatial organization of the genome within interphase nuclei is non-random. It has been shown that not only whole chromosomes but also individual genes occupy specific nuclear locations and these locations can be changed during different processes like differentiation or disease. Using a porcine in vitro adipogenesis stem cell differentiation system as a model to study nuclear organization, it was demonstrated that nuclear position of selected genes involved in porcine adipogenesis was altered with the up-regulation of gene expression, correlating with these genes becoming more internally located within nuclei, without whole territory relocation. Here, we investigated whether the gene relocation observed during porcine adipogenesis is related to spatial co-association with SC-35 domains. These domains are nuclear speckles enriched in numerous splicing and RNA metabolic factors. Using a DNA immuno-FISH approach we investigated the localisation of three adipogenic genes (PPARG, SREBF1, and FABP4) with SC-35 domains in porcine mesenchymal stem cells and after they were differentiated into adipocytes. We found that the location of these genes relative to SC-35 domains was non-random and correlated with the up-regulation of gene expression. In addition, we observed more frequent clustering of the studied genes located on different chromosomes around the same nuclear speckle in differentiated adipocytes than in mesenchymal stem cells. However, the choice of the domain was more random. This study adds to the evidence that SC-35 domains are hubs of gene activity and gene-domain association may be considered as a common mechanism to enhance gene expression.

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Abbreviations

3D:

Three-dimensional

AD14:

Differentiated adipocytes at day 14

FISH:

Fluorescence in situ hybridisation

MSC:

Mesenchymal stem cells

N2:

Nitrogen

PFA:

Paraformaldehyde

PBS:

Phosphate buffered saline

SSC:

Saline sodium citrate buffer

SSC:

Sus scrofa chromosome

References

  • Brown JM, Green J, das Neves RP, Wallace HA, Smith AJ, Hughes J, Gray N, Taylor S, Wood WG, Higgs DR, Iborra FJ, Buckle VJ (2008) Association between active genes occurs at nuclear speckles and is modulated by chromatin environment. J Cell Biol 82:1083–1097

    Article  Google Scholar 

  • Dundr M, Ospina JK, Sung MH, John S, Upender M, Ried T, Hager GL, Matera AG (2007) Actin-dependent intranuclear repositioning of an active gene locus in vivo. J Cell Biol 179:1095–1103

    Article  CAS  PubMed  Google Scholar 

  • Ferrai C, de Castro IJ, Lavitas L, Chotalia M, Pombo A (2010) Gene positioning. Cold Spring Harb Perspect Biol 2:a000588

    Article  PubMed  Google Scholar 

  • Finlan LE, Sproul D, Thomson I, Boyle S, Kerr E, Perry P, Ylstra B, Chubb JR, Bickmore WA (2008) Recruitment to the nuclear periphery can alter expression of genes in human cells. PLoS Genet 4:e1000039

    Article  PubMed  Google Scholar 

  • Hall LL, Smith KP, Byron M, Lawrence JB (2006) Molecular anatomy of a speckle. Anat Rec A Discov Mol Cell Evol Biol 288:664–675

    PubMed  Google Scholar 

  • Hu Q, Kwon YS, Nunez E, Cardamone MD, Hutt KR, Ohgi KA, Garcia-Bassets I, Rose DW, Glass CK, Rosenfeld MG, Fu XD (2008) Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules. Proc Natl Acad Sci USA 105:19199–19204

    Article  CAS  PubMed  Google Scholar 

  • Hu Y, Kireev I, Plutz M, Ashourian N, Belmont AS (2009) Large-scale chromatin structure of inducible genes: transcription on a condensed, linear template. J Cell Biol 185:87–100

    Article  CAS  PubMed  Google Scholar 

  • Johnson CV, Primorac D, McKinstry M, McNeil JA, Rowe D, Lawrence JB (2000) Tracking COL1A1 RNA in osteogenesis imperfecta: splice-defective transcripts initiate transport from the gene but are retained within the SC-35 domain. J Cell Biol 150:417–432

    Article  CAS  PubMed  Google Scholar 

  • Jolly C, Vourc’h C, Robert-Nicoud M, Morimoto RI (1999) Intron-independent association of splicing factors with active genes. J Cell Biol 145:1133–1143

    Article  CAS  PubMed  Google Scholar 

  • Kim SH, McQueen PG, Lichtman MK, Shevach EM, Parada LA, Misteli T (2004) Spatial genome organization during T-cell differentiation. Cytogenet Genome Res 105:292–301

    Article  CAS  PubMed  Google Scholar 

  • Kosak ST, Skok JA, Medina KL, Riblet R, Le Beau MM, Fisher AG, Singh H (2002) Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science 296:158–162

    Article  CAS  PubMed  Google Scholar 

  • Lamond AI, Spector DL (2003) Nuclear speckles: a model for nuclear organelles. Nat Rev Mol Cell Biol 4:605–612

    Article  CAS  PubMed  Google Scholar 

  • Meaburn KJ, Misteli T (2008) Locus-specific and activity-independent gene repositioning during early tumorigenesis. J Cell Biol 180:39–50

    Article  CAS  PubMed  Google Scholar 

  • Mehta IS, Amira M, Harvey AJ, Bridger JM (2010) Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts. Genome Biol 11:R5

    Article  PubMed  Google Scholar 

  • Moen PT Jr, Johnson CV, Byron M, Shopland LS, de la Serna IL, Imbalzano AN, Lawrence JB (2004) Repositioning of muscle-specific genes relative to the periphery of SC-35 domains during skeletal myogenesis. Mol Biol Cell 15:197–206

    Article  CAS  PubMed  Google Scholar 

  • Nielsen JA, Hudson LD, Armstrong RC (2002) Nuclear organization in differentiating oligodendrocytes. J Cell Sci 115:4071–4079

    Article  CAS  PubMed  Google Scholar 

  • Osborne CS, Chakalova L, Brown KE, Carter D, Horton A, Debrand E, Goyenechea B, Mitchell JA, Lopes S, Reik W, Fraser P (2004) Active genes dynamically colocalize to shared sites of ongoing transcription. Nat Genet 36:1065–1071

    Article  CAS  PubMed  Google Scholar 

  • Osborne CS, Chakalova L, Mitchell JA, Horton A, Wood AL, Bolland DJ, Corcoran AE, Fraser P (2007) Myc dynamically and preferentially relocates to a transcription factory occupied by Igh. PLoS Biol 5:e192

    Article  PubMed  Google Scholar 

  • Ragoczy T, Bender MA, Telling A, Byron R, Groudine M (2006) The locus control region is required for association of the murine beta-globin locus with engaged transcription factories during erythroid maturation. Genes Dev 20:1447–1457

    Article  CAS  PubMed  Google Scholar 

  • Reddy KL, Zullo JM, Bertolino E, Singh H (2008) Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 452:243–247

    Article  CAS  PubMed  Google Scholar 

  • Shopland LS, Johnson CV, Byron M, McNeil J, Lawrence JB (2003) Clustering of multiple specific genes and gene-rich R-bands around SC-35 domains: evidence for local euchromatic neighborhoods. J Cell Biol 162:981–990

    Article  CAS  PubMed  Google Scholar 

  • Smith KP, Moen PT, Wydner KL, Coleman JR, Lawrence JB (1999) Processing of endogenous pre-mRNAs in association with SC-35 domains is gene specific. J Cell Biol 144:617–629

    Article  CAS  PubMed  Google Scholar 

  • Smith KP, Byron M, Johnson C, Xing Y, Lawrence JB (2007) Defining early steps in mRNA transport: mutant mRNA in myotonic dystrophy type I is blocked at entry into SC-35 domains. J Cell Biol 178:951–964

    Article  CAS  PubMed  Google Scholar 

  • Szczerbal I, Foster HA, Bridger JM (2009) The spatial repositioning of adipogenesis genes is correlated with their expression status in a porcine mesenchymal stem cell adipogenesis model system. Chromosoma 118:647–663

    Article  CAS  PubMed  Google Scholar 

  • Takizawa T, Gudla PR, Guo L, Lockett S, Misteli T (2008a) Allele-specific nuclear positioning of the monoallelically expressed astrocyte marker GFAP. Genes Dev 22:489–498

    Article  CAS  PubMed  Google Scholar 

  • Takizawa T, Meaburn KJ, Misteli T (2008b) The meaning of gene positioning. Cell 135:9–13

    Article  CAS  PubMed  Google Scholar 

  • Williams RR, Azuara V, Perry P, Sauer S, Dvorkina M, Jørgensen H, Roix J, McQueen P, Misteli T, Merkenschlager M, Fisher AG (2006) Neural induction promotes large-scale chromatin reorganisation of the Mash1 locus. J Cell Sci 119:132–140

    Article  CAS  PubMed  Google Scholar 

  • Xing Y, Johnson CV, Moen PT, McNeil JA, Lawrence J (1995) Nonrandom gene organization: structural arrangements of specific pre-mRNA transcription and splicing with SC-35 domains. J Cell Biol 131:1635–1647

    Article  CAS  PubMed  Google Scholar 

  • Xu M, Cook PR (2008) Similar active genes cluster in specialized transcription factories. J Cell Biol 181:615–623

    Article  CAS  PubMed  Google Scholar 

  • Zeng C, Kim E, Warren SL, Berget SM (1997) Dynamic relocation of transcription and splicing factors dependent upon transcriptional activity. EMBO J 16:1401–1412

    Article  CAS  PubMed  Google Scholar 

  • Zink D, Amaral MD, Englmann A, Lang S, Clarke LA, Rudolph C, Alt F, Luther K, Braz C, Sadoni N, Rosenecker J, Schindelhauer D (2004) Transcription-dependent spatial arrangements of CFTR and adjacent genes in human cell nuclei. J Cell Biol 166:815–825

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

This study was financed by the Polish Ministry of Science and Higher Education, grant N301 3381 33.

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Authors and Affiliations

  1. Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Wolynska 33, 60-637, Poznan, Poland

    Izabela Szczerbal

  2. Laboratory of Nuclear and Genomic Health, Centre for Cell & Chromosome Biology, Biosciences, School of Health Sciences and Social Care, Brunel University, West London, UB8 3PH, UK

    Joanna M. Bridger

Authors
  1. Izabela Szczerbal
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  2. Joanna M. Bridger
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Correspondence to Izabela Szczerbal.

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Responsible Editor: Pat Heslop-Harrison.

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Szczerbal, I., Bridger, J.M. Association of adipogenic genes with SC-35 domains during porcine adipogenesis. Chromosome Res 18, 887–895 (2010). https://doi.org/10.1007/s10577-010-9176-1

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  • DOI: https://doi.org/10.1007/s10577-010-9176-1

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